Dendritic Ca2+ Signaling in Substantia Nigra Dopamine Neuron Subpopulations
Rebekah Evans, Manhua Zhu and Zayd Khaliq National Institute of Neurological Disorders and Stroke, NIH
Midbrain dopaminergic neurons play a critical role in a range of behaviors including voluntary movements, reward learning, aversion and cognition. Although early studies considered dopamine neurons to be a homogenous population, recent work has revealed that they are differentiated by axonal projection pattern, co-release of neurotransmitter, electrophysiological characteristics, expression of molecular markers, and responses during behavior. I will discuss our recent findings that focus on physiologically distinct subpopulations of dopaminergic neurons within the substantia nigra (SNc). While dopamine is known to inhibit action potential backpropagation into dendrites, our experiments reveal an unexpected enhancement of excitatory responses and dendritic calcium signals in the presence of D2-receptor inhibition. Specifically, dopamine inhibition and direct hyperpolarization enabled the generation low-threshold depolarizations that result from recruitment of T-type calcium channels. Interestingly, these effects occurred selectively in calbindin-negative SNc dopaminergic neurons, which are vulnerable to cell death in patients with Parkinson's Disease. Therefore, the hyperpolarization-dependent enhancement that we observe could promote the efficacy of excitatory inputs onto Calb- SNc neurons, which may be important for maintaining tonic spiking activity and proper motor function in the presence of high dopamine autoinhibition. Furthermore, these experiments demonstrate that calbindin-positive and negative SNc neurons differ substantially in their calcium channel composition, which may be relevant to a prominent hypothesis that identifies intracellular calcium as a potential source of excitotoxicity in Parkinson's Disease.
This work was supported by NINDS Intramural Research Program Grant NS00313